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MicroRNA Microarray Identifies Let-7i as a Novel Biomarker and Therapeutic Target in Human Epithelial Ovarian Cancer

NUO YANG ; KAUR, Sippy ; JOHNSTONE, Cameron N ; CHEN, Xian-Ming ; LIU, Chang-Gong ; QIHONG HUANG ; KATSAROS, Dionyssios ; CALIN, George Adrian ; WEBER, Barbara L ; BÜTZOW, Ralf ; CROCE, Carlo M ; COUKOS, George ; VOLINIA, Stefano ; LIN ZHANG ; GRESHOCK, Joel ; LASSUS, Heini ; HASEGAWA, Kosei ; SHUN LIANG ; LEMINEN, Arto ; SHAN DENG ; SMITH, Lori

Cancer research (Chicago, Ill.), 2008-12, Vol.68 (24), p.10307-10314 [Periódico revisado por pares]

Philadelphia, PA: American Association for Cancer Research

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Título:
MicroRNA Microarray Identifies Let-7i as a Novel Biomarker and Therapeutic Target in Human Epithelial Ovarian Cancer
Autor: NUO YANG ; KAUR, Sippy ; JOHNSTONE, Cameron N ; CHEN, Xian-Ming ; LIU, Chang-Gong ; QIHONG HUANG ; KATSAROS, Dionyssios ; CALIN, George Adrian ; WEBER, Barbara L ; BÜTZOW, Ralf ; CROCE, Carlo M ; COUKOS, George ; VOLINIA, Stefano ; LIN ZHANG ; GRESHOCK, Joel ; LASSUS, Heini ; HASEGAWA, Kosei ; SHUN LIANG ; LEMINEN, Arto ; SHAN DENG ; SMITH, Lori
Assuntos: Adult ; Aged ; Aged, 80 and over ; Antineoplastic agents ; Biological and medical sciences ; Biomarkers, Tumor - biosynthesis ; Biomarkers, Tumor - genetics ; Cisplatin - pharmacology ; DNA, Neoplasm - genetics ; Drug Resistance, Neoplasm ; Female ; Female genital diseases ; Gene Dosage ; Gynecology. Andrology. Obstetrics ; Humans ; Medical sciences ; MicroRNAs - biosynthesis ; MicroRNAs - genetics ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - metabolism ; Pharmacology. Drug treatments ; RNA, Messenger - genetics ; Tumors ; Young Adult
É parte de: Cancer research (Chicago, Ill.), 2008-12, Vol.68 (24), p.10307-10314
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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N. Yang, S. Kaur, S. Volinia, and J. Greshock contributed equally to this work.
Descrição: MicroRNAs (miRNA) are approximately 22-nucleotide noncoding RNAs that negatively regulate protein-coding gene expression in a sequence-specific manner via translational inhibition or mRNA degradation. Our recent studies showed that miRNAs exhibit genomic alterations at a high frequency and their expression is remarkably deregulated in ovarian cancer, strongly suggesting that miRNAs are involved in the initiation and progression of this disease. In the present study, we performed miRNA microarray to identify the miRNAs associated with chemotherapy response in ovarian cancer and found that let-7i expression was significantly reduced in chemotherapy-resistant patients (n = 69, P = 0.003). This result was further validated by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.015). Both loss-of-function (by synthetic let-7i inhibitor) and gain-of-function (by retroviral overexpression of let-7i) studies showed that reduced let-7i expression significantly increased the resistance of ovarian and breast cancer cells to the chemotherapy drug, cis-platinum. Finally, using miRNA microarray, we found that decreased let-7i expression was significantly associated with the shorter progression-free survival of patients with late-stage ovarian cancer (n = 72, P = 0.042). This finding was further validated in the same sample set by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.001) and in an independent sample set by in situ hybridization (n = 53, P = 0.049). Taken together, our results strongly suggest that let-7i might be used as a therapeutic target to modulate platinum-based chemotherapy and as a biomarker to predict chemotherapy response and survival in patients with ovarian cancer.
Editor: Philadelphia, PA: American Association for Cancer Research
Idioma: Inglês

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MicroRNA Microarray Identifies Let-7i as a Novel Biomarker and Therapeutic Target in Human Epithelial Ovarian Cancer

Philadelphia, PA: American Association for Cancer Research

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